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Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia ( p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores ( p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Introduction: Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18 F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD., Methods: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion., Results: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions., Discussion: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment., Highlights: Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion., Competing Interests: The authors declare no conflicts of interest related to this research. The principal author confirms that all authors have read the manuscript, and the paper has not previously been published or is under consideration at another journal. The authors take full responsibility for the data, analyses, and interpretation, and the conduct of the research, and have full access to all the data and the right to publish it. All authors have agreed to the conditions noted on the authorship agreement form., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Mortality data from Europe and North America show a shorter life expectancy for people with multiple sclerosis (MS). It is not known if a similar mortality risk exists in the southern hemisphere. We analysed the mortality outcomes of a comprehensive New Zealand (NZ) MS cohort, 15 years postrecruitment., Methods: All participants of the nationwide 2006 NZ MS prevalence study were included and mortality outcomes were compared with life table data from the NZ population using classic survival analyses, standardised mortality ratios (SMRs) and excess death rates (EDRs)., Results: Of 2909 MS participants, 844 (29%) were deceased at the end of the 15-year study period. Median survival age for the MS cohort was 79.4 years (78.5, 80.3), compared with 86.6 years (85.5, 87.7) for the age-matched and sex-matched NZ population. The overall SMR was 1.9 (1.8, 2.1)). Symptom onset between 21 and 30 years corresponded to an SMR of 2.8 and a median survival age 9.8 years lower than the NZ population. Progressive-onset disease was associated with a survival gap of 9 years compared with 5.7 years for relapsing onset. The EDR for those diagnosed in 1997-2006 was 3.2 (2.6, 3.9) compared with 7.8 (5.8, 10.3) for those diagnosed between 1967 and 1976., Conclusions: New Zealanders with MS have a median survival age 7.2 years lower than the general population and twice the mortality risk. The survival gap was greater for progressive-onset disease and for those with an early age of onset., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited lysosomal storage disorders characterized by progressive neurodegeneration leading to motor and cognitive dysfunction, seizure activity and blindness. The disease can be caused by mutations in 1 of 13 ceroid lipofuscinosis neuronal (CLN) genes. Naturally occurring sheep models of the CLN5 and CLN6 neuronal ceroid lipofuscinoses recapitulate the clinical disease progression and post-mortem pathology of the human disease. We used longitudinal MRI to assess global and regional brain volume changes in CLN5 and CLN6 affected sheep compared to age-matched controls over 18 months. In both models, grey matter volume progressively decreased over time, while cerebrospinal fluid volume increased in affected sheep compared with controls. Total grey matter volume showed a strong positive correlation with clinical scores, while cerebrospinal fluid volume was negatively correlated with clinical scores. Cortical regions in affected animals showed significant atrophy at baseline (5 months of age) and progressively declined over the disease course. Subcortical regions were relatively spared with the exception of the caudate nucleus in CLN5 affected animals that degenerated rapidly at end-stage disease. Our results, which indicate selective vulnerability and provide a timeline of degeneration of specific brain regions in two sheep models of neuronal ceroid lipofuscinoses, will provide a clinically relevant benchmark for assessing therapeutic efficacy in subsequent trials of gene therapy for CLN5 and CLN6 disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aims: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown., Methods: During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown., Results: Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity., Conclusions: Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD., Competing Interests: Nil.

Background: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD., Objectives: Determine if neuropsychiatric symptoms are useful markers of PDD risk., Methods: 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD., Results: The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD., Conclusions: Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk., Competing Interests: The research conducted in this article was funded by research support from the New Zealand Health Research Council, Brain Research New Zealand—Rangahau Roro Aotearoa, University of Otago, University of Canterbury, Neurological Foundation of New Zealand, Canterbury Medical Research Foundation, and the New Zealand Brain Research Institute. The authors of this article have no financial relationships relevant to this article to disclose or conflicts of interest., (© 2021 International Parkinson and Movement Disorder Society.)

Background: Uncontrolled studies have reported associations between later Parkinson's disease onset in women and a history of giving birth, with age at onset delayed by nearly 3 years per child. We tested this association in two independent data sets, but, as a control to test for nonbiological explanations, also included men with PD., Methods: We analyzed valid cases from the Parkinson's Progressive Markers Initiative incident sample (145 women, 276 men) and a prevalent sample surveyed by the New Zealand Brain Research Institute (210 women, 394 men)., Results: The association was present in both women and men in the Parkinson's Progressive Markers Initiative study, and absent in both in the New Zealand Brain Research Institute study. This is consistent with generational differences common to men and women, which confound with age at onset in incident-dominant samples., Conclusions: Despite being replicable in certain circumstances, associations between childbirth and later PD onset are an artifact of generational cohort differences. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Objective: Many factors can contribute to the reliability and robustness of MRI-derived metrics. In this study, we assessed the reliability and reproducibility of three MRI modalities after an MRI scanner was relocated to a new hospital facility., Methods: Twenty healthy volunteers (12 females, mean age (standard deviation) ​= ​41 (11) years, age range [25-66]) completed three MRI sessions. The first session (S1) was one week prior to the 3T GE HDxt scanner relocation. The second (S2) occurred nine weeks after S1 and at the new location; a third session (S3) was acquired 4 weeks after S2. At each session, we acquired structural T1-weighted, pseudo-continuous arterial spin labelled, and diffusion tensor imaging sequences. We used longitudinal processing streams to create 12 summary MRI metrics, including total gray matter (GM), cortical GM, subcortical GM, white matter (WM), and lateral ventricle volume; mean cortical thickness; total surface area; average gray matter perfusion, and average diffusion tensor metrics along principal white matter pathways. We compared mean MRI values and variance at the old scanner location to multiple sessions at the new location using Bayesian multi-level regression models. K-fold cross validation allowed identification of important predictors. Whole-brain analyses were used to investigate any regional differences. Furthermore, we calculated within-subject coefficient of variation (wsCV), intraclass correlation coefficient (ICC), and dice similarity index (SI) of cortical segmentations across scanner relocation and within-site. Additionally, we estimated sample sizes required to robustly detect a 4% difference between two groups across MRI metrics., Results: All global MRI metrics exhibited little mean difference and small variability (bar cortical gray matter perfusion) both across scanner relocation and within-site repeat. T1- and DTI-derived tissue metrics showed ​< ​|0.3|% mean difference and <1.2% variance across scanner location and <|0.4|% mean difference and <0.8% variance within the new location, with between-site intraclass correlation coefficient (ICC) ​> ​0.80 and within-subject coefficient of variation (wsCV) ​< ​1.4%. Mean cortical gray matter perfusion had the highest between-session variability (6.7% [0.3, 16.7], estimate [95% uncertainty interval]), and hence the smallest ICC (0.71 [0.44,0.92]) and largest wsCV (13.4% [5.4, 18.1]). No global metric exhibited evidence of a meaningful mean difference between scanner locations. However, surface area showed evidence of a mean difference within-site repeat (between S2 and S3). Whole-brain analyses revealed no significant areas of difference between scanner relocation or within-site. For all metrics, we found no support for a systematic difference in variance across relocation sites compared to within-site test-retest reliability. Necessary sample sizes to detect a 4% difference between two independent groups varied from a maximum of n ​= ​362 per group (cortical gray matter perfusion), to total gray matter volume (n ​= ​114), average fractional anisotropy (n ​= ​23), total gray matter volume normalized by intracranial volume (n ​= ​19), and axial diffusivity (n ​= ​3 per group)., Conclusion: Cortical gray matter perfusion was the most variable metric investigated (necessitating large sample sizes to identify group differences), with other metrics showing substantially less variability. Scanner relocation appeared to have a negligible effect on variability of the global MRI metrics tested. This manuscript reports within-site test-retest variability to act as a tool for calculating sample size in future investigations. Our results suggest that when all other parameters are held constant (e.g., sequence parameters and MRI processing), the effect of scanner relocation is indistinguishable from within-site variability, but may need to be considered depending on the question being investigated., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We have observed in the clinic that a number of patients with Parkinson's disease (PD) can suppress their tremor at will for brief periods, by conscious mental processes. To our knowledge, the ability to consciously diminish one's resting tremor has not yet been reported nor assessed quantitatively., Objective: To provide the first detailed systematic investigation of the phenomenon of voluntary tremor suppression in PD., Methods: We examined changes in tremor characteristics during voluntary tremor suppression in 37 PD patients ( on medication) presenting with rest tremor in their upper limb. We measured tremor oscillations with a triaxis accelerometer on the index finger of the most-affected hand (n = 27). With surface electromyography (EMG), we measured changes in neuromuscular activity of the forearm flexor digitorum superficialis and extensor digitorum muscles (n = 15). Participants completed four 1-minute trials, consisting of alternating consecutive 30-second periods of resting tremor and 30-second periods of attempted tremor suppression., Results: Bayesian multilevel modeling revealed that attempted voluntary tremor suppression did indeed reduce tremor amplitude (peak power) of the acceleration signal and increased tremor frequency of the acceleration and EMG signals. Relative EMG power in the 3- to 8-Hz tremor band was also smaller. Tremor suppression was not by enhanced voluntary contraction of the relevant muscle pairs., Conclusions: We present novel empirical evidence that PD resting tremor can be suppressed by an act of will, as evidenced by significant modulation of key neurophysiological tremor characteristics. These data highlight that it is possible to exert significant conscious control over parkinsonian resting tremor., Competing Interests: This work was supported by a Neurological Foundation of New Zealand Project Grant (1540‐PG to R.L.B.) and the New Zealand Brain Research Institute. The authors declare that there are no conflicts of interest relevant to this work.

The extent to which Alzheimer neuropathology, particularly the accumulation of misfolded beta-amyloid, contributes to cognitive decline and dementia in Parkinson's disease (PD) is unresolved. Here, we used Florbetaben PET imaging to test for any association between cerebral amyloid deposition and cognitive impairment in PD, in a sample enriched for cases with mild cognitive impairment. This cross-sectional study used Movement Disorders Society level II criteria to classify 115 participants with PD as having normal cognition (PDN, n = 23), mild cognitive impairment (PD-MCI, n = 76), or dementia (PDD, n = 16). We acquired 18F-Florbetaben (FBB) amyloid PET and structural MRI. Amyloid deposition was assessed between the three cognitive groups, and also across the whole sample using continuous measures of both global cognitive status and average performance in memory domain tests. Outcomes were cortical FBB uptake, expressed in centiloids and as standardized uptake value ratios (SUVR) using the Centiloid Project whole cerebellum region as a reference, and regional SUVR measurements. FBB binding was higher in PDD, but this difference did not survive adjustment for the older age of the PDD group. We established a suitable centiloid cut-off for amyloid positivity in Parkinson's disease (31.3), but there was no association of FBB binding with global cognitive or memory scores. The failure to find an association between PET amyloid deposition and cognitive impairment in a moderately large sample, particularly given that it was enriched with PD-MCI patients at risk of dementia, suggests that amyloid pathology is not the primary driver of cognitive impairment and dementia in most patients with PD.

Background: New Zealand is an ethnically diverse country with a unified national prescribing system. This provides a good framework to use drug-tracing methodology to establish the prevalence and incidence of Parkinson's disease across different ethnic groups. The objective of this study was to determine the prevalence and incidence of Parkinson's disease in the major ethnic groups in New Zealand., Methods: Information on Parkinson's disease-related medications was extracted from the national Pharmaceutical Collection of community-dispensed medications for the period January 1, 2005, to December 31, 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions data sets. We used a Bayesian model, accommodating uncertainty and bias, to estimate the number of people with Parkinson's disease., Results: We found the highest rate of Parkinson's disease in the European ethnic group and the lowest rate in the indigenous Māori. The 2006-2013 age-standardized incidence (per 100,000 population per year) was European, 33; Asian, 28; Pasifika, 27; Māori, 20. The 2013 age-standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Māori, 114., Conclusions: There is a differential occurrence of Parkinson's disease across the major ethnic groups within the New Zealand population, with indigenous Māori showing the lowest incidence. Varying susceptibility profiles, gene-environment interactions, and inequalities in accessing health care may play a role in the variation in rates of Parkinson's disease in New Zealand. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Background: Traditionally the risk of Parkinson's has been considered to increase monotonically with age, although there is evidence that prevalence and incidence may decrease in the oldest old. To examine this further we estimated the national prevalence and incidence of Parkinson's in New Zealand, using drug-tracing methods, to examine the relationship of Parkinson's with sex and age up to 100+., Methods: Information on Parkinson's-related medications was extracted from the national pharmaceutical database of community-dispensed medications from 2005 to 2014. Diagnoses for a large subset of individuals were independently determined through national mortality and hospital admissions datasets. We used a Bayesian model, accommodating diagnostic uncertainty and bias, to estimate the number of people with Parkinson's., Results: The 2013 prevalence of Parkinson's in New Zealand was 210 per 100 000 population (95% uncertainty interval 208-212) with age-standardized prevalence rates higher for males (ratio 1.6:1). Incidence was 31 per 100 000 person-years (95% uncertainty interval 30-32), also higher in males (ratio 1.8:1). Incidence and prevalence by age increased exponentially until 75 years, peaked at 85 years, and then dropped sharply., Conclusions: The prevalence of Parkinson's in New Zealand is expected to double over a 25-year period but then increase at a slower rate due to the drop-off in prevalence and incidence in the oldest old. The findings suggest that Parkinson's disease is not an aging-dependent but an age-dependent disorder., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The Movement Disorder Society Task Force (MDS-TF) has proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI). We hypothesized that the risk of dementia (PDD) varies across the different cutoff schemes allowed. A longitudinal study followed 121 non-demented PD patients for up to 4.5 years. In Part One, unique groups of patients were identified as PD-MCI at baseline using the MDS-TF requirement of two impaired cognitive test scores, with both scores classified as impaired at either (i) 2 s.d., (ii) 1.5 s.d. or (iii) 1 s.d. below normative data; relative risk (RR) of PDD was assessed at each criterion. In Part Two, the whole sample was reassessed and (i) RR of PDD determined when two impairments at 1.5 s.d. existed within a single cognitive domain, followed by (ii) RR of PDD in the unique group whose two impairments at 1.5 s.d. did not exist within a single domain (i.e., only across two domains). Twenty-one percent of patients converted to PDD. Part One showed that the 1.5 s.d. criterion at baseline is optimal to maximize progression to PDD over 4 years. Part Two, however, showed that the 1.5 s.d. cutoff produced a high RR of PDD only when two impairments were identified within a single cognitive domain (7.2, 95% confidence interval (CI)=3.4-16.6, P <0.0001; 51% converted). The RR when the 1.5 s.d. impairments occurred only across two different domains, was nonsignificant (1.7, CI=0.5-7.4, P =0.13; 11% converted) and similar to using a 1 s.d. criterion (1.9, CI=0.3-4.3, P =0.13; 8% converted). If the intent of a PD-MCI diagnosis is to detect increased risk of PDD in the next 4 years, optimal criteria should identify at least two impairments at 1.5 s.d. within a single cognitive domain., Competing Interests: The authors declare no conflict of interest.

Introduction: Parkinson's Disease (PD) is classified as a motor disorder, but most patients develop cognitive impairment, and eventual dementia (PDD). Predictive neurobiomarkers may be useful in the identification of those patients at imminent risk of PDD. Given the compromised cerebral integrity in PDD, we investigated whether brain metabolites track disease progression over time., Methods: Proton Magnetic Resonance Spectroscopy (MRS) was used to identify brain metabolic changes associated with cognitive impairment and dementia in PD. Forty-nine healthy participants and 130 PD patients underwent serial single voxel proton MRS and neuropsychological testing. At baseline patients were classified as either having normal cognitive status (PDN, n = 77), mild cognitive impairment (PDMCI, n = 33), or dementia (PDD, n = 20). Posterior cingulate cortex (PCC) was examined to quantify N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI). A hierarchical Bayesian model was used to assess whether cognitive ability and other covariates were related to baseline MRS values and changes in MRS over time., Results: At baseline, relative to controls, PDD had significantly decreased NAA/Cr and increased Cho/Cr. However, these differences did not remain significant after accounting for age, sex, and MDS-UPDRS III. At follow-up, no significant changes in MRS metabolite ratios were detected, with no relationship found between MRS measures and change in cognitive status., Conclusions: Unlike Alzheimer's disease, single voxel MR spectroscopy of the PCC failed to show any significant association with cognitive status at baseline or over time. This suggests that MRS of PCC is not a clinically useful biomarker for tracking or predicting cognitive impairment in Parkinson's disease., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background & Objectives: Cross-sectional magnetic resonance imaging (MRI) suggests that Parkinson's disease (PD) is associated with changes in cerebral tissue volume, diffusion tensor imaging metrics, and perfusion values. Here, we performed a longitudinal multimodal MRI study--including structural, diffusion tensor imaging (DTI), and perfusion MRI--to investigate progressive brain changes over one year in a group of older PD patients at a moderate stage of disease., Methods: Twenty-three non-demented PD (mean age (SD) = 69.5 (6.4) years, disease duration (SD) = 5.6 (4.3) years) and 23 matched control participants (mean age: 70.6 (6.8)) completed extensive neuropsychological and clinical assessment, and multimodal 3T MRI scanning at baseline and one year later. We used a voxel-based approach to assess change over time and group-by-time interactions for cerebral structural and perfusion metrics., Results: Compared to controls, in PD participants there was localized grey matter atrophy over time in bilateral inferior and right middle temporal, and left orbito-frontal cortices. Using a voxel-based approach that focused on the centers of principal white matter tracts, the PD and control cohorts exhibited similar levels of change in DTI metrics. There was no significant change in perfusion, cognitive, or motor severity measures., Conclusions: In a cohort of older, non-demented PD participants, macrostructural MRI detected atrophy in the PD group compared with the control group in temporal and orbito-frontal cortices. Changes in diffusion MRI along principal white matter tracts over one year were found, but this was not differentially affected by PD.

Progressive cognitive decline is a feature of Huntington's disease (HD), an inherited neurodegenerative movement disorder. Comprehensive neuropsychological testing is the 'gold standard' to establish cognitive status but is often impractical in time-constrained clinics. The study evaluated the utility of brief cognitive tests (MMSE and MoCA), UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in HD. Twenty-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month. A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months, they did show a significant decline relative to the control group. The controls exhibited a practice effect in most of the cognitive domain scores over time. Cognitive decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain score. The varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive score. The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis. The UHDRS cognitive component, which focuses on testing executive function and had low variance over time, is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months.

Emerging evidence suggests that Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer's disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD

Changes in morphometry of head and neck muscles have received little attention in research relative to limb muscles. While recent literature suggests that high-frequency ultrasound transducers can provide superior spatial resolution compared to that of magnetic resonance imaging (MRI), no studies have compared these imaging methods for investigating the submental muscle group. This preliminary study sought to compare ultrasound and MRI as a method of quantifying the cross-sectional area (CSA) of the submental muscle group. Measurements were taken from coronal ultrasound and MRI images in 11 healthy participants. Comparisons were limited to the anterior belly of the digastric muscle because of differences in imaging resolution. Ultrasound CSA measurements were smaller than MRI measurements (p = 0.01) by 10 % (95% CI = -18 to -2). Correlations were significant and relatively high (left: r = 0.909, p < 0.001; right: r = 0.776, p = 0.005). Ultrasound imaging has the advantages of natural participant positioning, superior clarity of muscle borders of the submental muscles, requires less acquisition time, and is a less expensive method of imaging compared to MRI. This preliminary study has shown that ultrasound is a viable imaging modality for quantitative measurements of the anterior belly of the digastric muscle and has advantages over MRI beyond cost and accessibility.

Studies of saccades in Parkinson's disease (PD) have seldom examined the influence of cognitive status, ranging from normal cognition, through mild cognitive impairment, to dementia. In a large and heterogeneous sample, we examined how motor and cognitive impairment was reflected in the performance of reflexive, visually-guided saccades. We examined 163 people with PD and 47 similar-aged controls. Ninety three of the PD group had normal cognition (PDN), 48 had mild cognitive impairment (PD-MCI), and 22 had dementia (PDD). Pseudo-random targets (amplitudes of 5, 10, 15 and 20 deg and inter-stimulus-intervals ranging from 550 to 1800 ms) were shown in 108 mixed randomised trials, incorporating gap, step, and overlap onset conditions. Analyses were conducted using multi-level regression modeling. Participants were first assessed by continuous measures (Unified PD Rating Scale motor score and the Montreal Cognitive Assessment). Prolonged latency was significantly related to both motor and cognitive impairment, with the cognitive effect being compounded by increasing age. Decreased saccade amplitude, meanwhile, was primarily related to motor impairment. When assessed by discrete cognitive categories, all of the PD groups showed reduced saccadic amplitude relative to controls. Saccadic latencies, meanwhile, were abnormally prolonged only in the PD-MCI and PDD groups (the control and PDN groups were similar to each other). Latency in the overlap task was particularly sensitive to increasing motor and cognitive impairment. We conclude that reflexive saccades in PD are subtly decreased in amplitude even early in the disease process. Prolonged saccade latency, meanwhile, tends to occur later in the disease process, in the presence of more substantial motor and cognitive impairment, and greater age. The progressive impairment of reflexive saccades, and the differential onset of amplitude and latency impairments, may make them a useful objective tool for assessing disease status., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

No studies have investigated within-subject variation in measures of pharyngeal pressures during swallowing across sessions. This study aimed to document the variation in pharyngeal pressures both within and across three sessions. Twenty healthy participants were recruited for three sessions. For each session, peak or nadir pressures were recorded from the upper pharynx (sensor 1), mid-pharynx (sensor 2), and upper esophageal sphincter (sensor 3) during saliva and 10-ml water bolus swallows. Variance was larger across sessions than within sessions for sensors 1 and 2 but comparable for sensor 3. For all sensors there was a high correlation between the variance across sessions and within session (r = 0.92, p < 0.0001). There were no significant order effects of session or of trial at any sensor with estimated order effects less than 2% and the estimated maximum possible change no larger than 5% for trial and no larger than 12% for session. These data offer direction for longitudinal treatment studies in which pharyngeal pressures are an outcome measurement by (1) providing a basis for power calculations, (2) estimating the likely values of any confounding order effects, and (3) providing suggestions for more reliable data analysis.

We have developed a modular virtual environment platform for movement research and rehabilitation. The system uses several networked computers running Linux to share computation. An electromagnetic tracker is the primary position tracker and both a head-mounted display and stereo goggles are used for visual display. System software is written in a combination of C++, JAVA, and Python and makes considerable use of the open-source toolkits VR Juggler and OpenSceneGraph. These are integrated with additional toolkits and custom modules written specifically for the study of motor control and rehabilitation. The system performs well with low latency, accurate calibration, and a consistently high graphics update rate. Preliminary applications have confirmed that the system is a powerful tool for sensory-motor investigation and has considerable potential as a tool for neurorehabilitation. Its primary advantage over other systems is its ability to utilize different display and input devices, and run a range of experiments simply by changing XML configuration files. Additionally, the use of powerful open-source libraries provides a feature-rich foundation for advanced features and low-cost duplication. Further work and experiments are needed to extend, further validate, and fully utilize this platform.

Movements in people with Parkinson's disease are often hypometric, although we have found that this was not the case in an experimental visually-guided reaching task. We wished to explore our hypotheses that (1) people with Parkinson's disease produce hypometric primary submovements but(2) are able to use visual feedback to accurately reach the target in a single overall movement, and (3) this effect may be greater in memory-guided tasks in which an internal representation of the target location is used instead of a fixation-centered representation of the target.Visually- and memory-guided reaching movements were examined in 22 people with mild to moderate severity Parkinson's disease on medication, along with age-matched and sex-matched controls. Primary submovements were extracted from 5149 movements using a method based upon zero crossings of jerk(3rd derivative of position), with several additional criteria to minimize the detection of submovements due to noise or tremor.There was no difference in the end position of the overall reaching movement between the two groups, although the movement was smaller in the memory-guided task. In contrast,the gain of the primary submovement was smaller in the Parkinson's disease group than the control group, with this difference being greater on the memory-guided task. There was no task effect on the primary submovement gain in the control group.Our results show that the underlying primary submovement in visually-guided movements in people with Parkinson's disease is hypometric, and that the degree of hypometria is even greater in memory-guided movements.

The fractal dimension (FD) of EEG has been shown to be of value in the detection of epileptic seizures. In this paper, we assess its usefulness in detecting behavioural microsleeps. Fifteen non-sleep-deprived normal subjects performed two 1-hour sessions of a continuous tracking task while EEG, EOG and facial video were recorded. Higuchi's algorithm was used to calculate the FD of the EEG. Video lapses were scored independently from tracking performance by a human rater. A subset of data was rated independently by three human raters observing both tracking performance and the video rating to identify behavioural microsleep events. The mean point-biserial correlation between FD and the mean human rating was -0.213 indicating modest agreement. Crossvalidated detection performance of the FD was poor with a mean correlation (.. = -0.099). This suggests that, on its own, FD of the EEG is unlikely to be useful for detecting microsleeps.